Nerve growth factor stimulates protein kinase C translocation in PC12 cells

Kondratyev, A.D.; Popova, O.N.; Северин, С. Е.; Choladze, M.A.; Shmyrev, I. I.; Tubasheva, I. A.; Zotova, Elina; Посыпанова, Г. А.; Severin, E S

doi:10.1016/0014-5793(90)80768-e

Cited by 25 publications

(20 citation statements)

References 21 publications

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“…These results suggest that phosphorylation of SNAP-25 by some types of PKC may be involved in NGF-induced neurite outgrowth. It is interesting that NGF-induced protein translocation from cytoplasm to plasma membrane is also reported in PKC itself (Kondratyev et al, 1990) and in GAP-43 (Van Hooff et al, 1989). It will be interesting to study relationships between protein translocation and neurite extension to gain an insight into the molecular mechanisms of neuronal differentiation.…”

Section: Figmentioning

confidence: 94%

Nerve Growth Factor‐Induced Phosphorylation of SNAP‐25 in PC12 Cells

Kataoka

Kuwahara

Iwasaki

et al. 2000

Journal of Neurochemistry

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Synaptosomal-associated protein of 25 kDa (SNAP-25), a t-SNARE protein essential for neurotransmitter release, is phosphorylated at Ser 187 following activation of cellular protein kinase C by treatment with phorbol 12-myristate 13-acetate. However, it remains unclear whether neuronal activity or an endogenous ligand induces the phosphorylation of SNAP-25. Here we studied the phosphorylation of SNAP-25 in PC12 cells using a specific antibody for SNAP-25 phosphorylated at Ser 187 . A small fraction of SNAP-25 was phosphorylated when cells were grown in the absence of nerve growth factor (NGF). A brief treatment with NGF that was enough to activate the mitogen-activated protein kinase signal transduction pathway did not increase the phosphorylation of SNAP-25; however, phosphorylation was up-regulated after a prolonged incubation with NGF. Up-regulation was transitory, and maximum phosphorylation (a fourfold increase over basal phosphorylation) was achieved between 36 and 48 h after the addition of NGF. Immunofluorescent microscopy showed that SNAP-25 was localized primarily in the plasma membrane, although a significant population was also present in the cytoplasm. Quantitative microfluorometry revealed that prolonged treatment with NGF resulted in a preferential localization of SNAP-25 in the plasma membrane. A mutational study using a fusion protein with green fluorescent protein as a tag indicated that the point mutation of Ser 187 to Ala abolished the NGF-dependent relocalization. A population of SNAP-25 in the plasma membrane was not increased by a point mutation at Ser 187 to Glu; however, it was increased by prolonged treatment with NGF, indicating that the SNAP-25 phosphorylation is essential, but not sufficient, for the NGF-induced relocation to the plasma membrane. Our results suggest a close temporal relationship between the up-regulation of SNAP-25 phosphorylation and its relocation, and NGF-induced differentiation of PC12 cells. Key Words: SNAP-25-Phosphorylation-Localization-Nerve growth factor-PC12. J. Neurochem. 74, 2058Neurochem. 74, -2066Neurochem. 74, (2000.Plasticity of neuronal networks in the brain is essential for learning and memory, and their cellular basis is believed to be the modulation of the strength and/or number of synaptic contacts (Bailey and Kandel, 1993).Numerous studies suggest that the regulation of synaptic strength can be controlled by protein phosphorylation through kinases and phosphatases; however, the precise mechanisms, including the identification of the relevant protein substrates of these enzymes, are still poorly understood. Many proteins participate in various synaptic functions and are substrates for several protein kinases Nielander et al., 1995;Hirling and Scheller, 1996;Risinger and Bennett, 1999). Synaptosomal-associated protein of 25 kDa (SNAP-25) is a membrane protein expressed in neurons and endocrine cells (Oyler et al., 1989). In neurons, SNAP-25 is localized primarily in axons and nerve terminals, and a large part of SNAP-25 is associated ...

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Section: Figmentioning

confidence: 94%

Nerve Growth Factor‐Induced Phosphorylation of SNAP‐25 in PC12 Cells

Kataoka

Kuwahara

Iwasaki

et al. 2000

Journal of Neurochemistry

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“…Additional previous studies of short-term (less than 1 h) NGF-treated PC12 cells have demonstrated the translocation to the particulate subcellular fraction of PKCa (Kondratyev et al, 1990) and PKCQ (Wooten et al, 1994), and a selective activation of PKCE kinase activity (Ohmichi et al, 1993). These rapid effects may be related to the early signal transduction events initiated by NGF binding to the Trk proto-oncogene receptor expressed in PC12 cells (Kaplan et al, 1991); however, because NGF-induced neuritogenesis by PC12 cells occurs over a prolonged course (1-7 days) (Greene and Tischler, 1976), in the present study we examined the expression of several PKC isoforms at later time points.…”

Section: Ngf Differentially Regulates Individual Pkc Isoforms In Pc12mentioning

confidence: 95%

Selective translocation of protein kinase C-delta in PC12 cells during nerve growth factor-induced neuritogenesis.

O’Driscoll¹,

Teng²,

Fabbro³

et al. 1995

MBoC

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The specific intracellular signals initiated by nerve growth factor (NGF) that lead to neurite formation in PC12 rat pheochromocytoma cells are as of yet unclear. Protein kinase C-delta (PKC delta) is translocated from the soluble to the particulate subcellular fraction during NGF-induced-neuritogenesis; however, this does not occur after treatment with the epidermal growth factor, which is mitogenic but does not induce neurite formation. PC12 cells also contain both Ca(2+)-sensitive and Ca(2+)-independent PKC enzymatic activities, and express mRNA and immunoreactive proteins corresponding to the PKC isoforms alpha, beta, delta, epsilon, and zeta. There are transient decreases in the levels of immunoreactive PKCs alpha, beta, and epsilon after 1-3 days of NGF treatment, and after 7 days there is a 2.5-fold increase in the level of PKC alpha, and a 1.8-fold increase in total cellular PKC activity. NGF-induced PC12 cell neuritogenesis is enhanced by 12-O-tetradecanoyl phorbol-13-acetate (TPA) in a TPA dose- and time-dependent manner, and this differentiation coincides with abrogation of the down-regulation of PKC delta and other PKC isoforms, when the cells are treated with TPA. Thus a selective activation of PKC delta may play a role in neuritogenic signals in PC12 cells.

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“…PKC activators, such as phorbol esters, mimic certain biological activities of NGF in PC12 cells (9,10). In addition, NGF has been shown to stimulate translocation of PKC activity and activation of specific isoforms (11,12). Likewise, certain NGF-specific transcripts are induced in response to PKC (13).…”

mentioning

confidence: 99%